In recent years, much interest has focused on the field of nanotechnology or “nano” as it is known.
In the field of nanotechnology, research and development is particularly active in the area of nano-biotechnology, which is a new field that merges semiconductor nanotechnology and biotechnology, as it may provide fundamental solutions to existing problems.
In this area of nano-biotechnology, DNA chips (or DNA microarrays) and other biochips, in which multiple different analytes of DNA, proteins or other biopolymers are spotted in high-density arrays on substrates formed of glass, silicon, plastic, metal and the like, are of interest as a way of simplifying nucleic acid and protein testing in the fields of clinical diagnosis, drug therapy and the like, and particularly an effective tool for gene analysis (T. G. Drummond et al., “Electrochemical DNA sensors”, Nature Biotech., 2003, Vol. 21, No. 10, p. 1192-1199; J. Wang, “Survey and summary from DNA biosensors to gene chips”, Nucleic Acids Research, 2000, Vol. 28, No. 16, p. 3011-3016).
In recent years, attention has focused on devices called “MEMS” and “μTAS”, which are prepared based on a technology for evaluating extremely small targets in which a functional molecule or a molecule bound to a functional molecule is bound to part of a solid substrate to form a functional surface (evaluation part), in combination with micromachining techniques and microsensing techniques, because they offer great improvements over conventional evaluation sensitivity and evaluation time. “MEMS” is an abbreviation for micro-electro mechanical systems, and signifies a technology for producing extremely small systems with semiconductor processing technology or a precise micro-machine prepared using this technology, or more generally a system in which the mechanical, optical, fluid and other functional parts are integrated and miniaturized. “μTAS” is an abbreviation for micro total analysis system, and signifies a small-scale, integrated analysis system of micropumps, microvalves, sensors and the like. These devices generally have functional surfaces with functional molecules having specific functions, or molecules bound to such functional molecules, fixed (bound) by self-organization on a substrate. Many methods are used for electrically or optically evaluating reactions on the functional surfaces of these devices.
Of these, optical evaluation methods are methods in which a target (object of evaluation) is modified with a fluorescent dye or other optical label, and is then evaluated quantitatively according to the optical intensity, and these methods are widely used in DNA chips and the like because of their high sensitivity.
However, these methods require a procedure of modifying the target with a label, and require complex steps such as labeling, washing and the like. Other problems include mis-detection due to contamination by the unattached label, and evaluation of targets adsorbed non-specifically to the evaluation part rather than by specific binding with the probe.
Consequently, there is demand for development of highly selective, low-noise evaluation techniques that do not require the target to be labeled (non-label techniques), and that avoid mis-detection of non-specifically adsorbed targets and the like.
As a label-free method of evaluating a target molecule, a method is known in which a charged analyte is labeled with a marker, the analyte is fixed on an electrode and driven with an electric field, the motion of the analyte is monitored according to the signal from the marker, the motion of the analyte changes when the target molecule has bound specifically to the analyte, and this change is evaluated by means of the marker modifying the analyte (U. Rant et al., “Dynamic electrical switching of DNA layers on a metal surface”, Nano Lett., 2004, Vol. 4, No. 12, p. 2441-2445; Japanese Patent Application No. 2004-238696 (claims); U.S. Patent Application Publication No. 2005069932, claims). The principle is that the charged analyte is attracted to or repelled from the substrate surface by applied electric field, changing the distance between the substrate and the marker attached to the tip of the analyte, and resulting in changes in the signal from the marker that can be observed. As long as the driving frequency is in a frequency range (about 1 MHz or less) that allows formation of an electrical double layer as a source for the electric field, a target molecule can be evaluated by observing the signal from the marker, which is synchronized with the driving potential.